EP3173075A1 - Préparation pharmaceutique combinée constituée d'un inhibiteur ace et diurétique de l'anse - Google Patents
Préparation pharmaceutique combinée constituée d'un inhibiteur ace et diurétique de l'anse Download PDFInfo
- Publication number
- EP3173075A1 EP3173075A1 EP15003387.6A EP15003387A EP3173075A1 EP 3173075 A1 EP3173075 A1 EP 3173075A1 EP 15003387 A EP15003387 A EP 15003387A EP 3173075 A1 EP3173075 A1 EP 3173075A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- torasemide
- lisinopril
- pharmaceutical combination
- combination preparation
- preparation according
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 33
- 239000005541 ACE inhibitor Substances 0.000 title claims abstract description 7
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 title claims abstract description 7
- 239000002171 loop diuretic Substances 0.000 title claims abstract description 7
- NGBFQHCMQULJNZ-UHFFFAOYSA-N Torsemide Chemical compound CC(C)NC(=O)NS(=O)(=O)C1=CN=CC=C1NC1=CC=CC(C)=C1 NGBFQHCMQULJNZ-UHFFFAOYSA-N 0.000 claims abstract description 71
- 229960005461 torasemide Drugs 0.000 claims abstract description 71
- 229960002394 lisinopril Drugs 0.000 claims abstract description 61
- RLAWWYSOJDYHDC-BZSNNMDCSA-N lisinopril Chemical compound C([C@H](N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(O)=O)C(O)=O)CC1=CC=CC=C1 RLAWWYSOJDYHDC-BZSNNMDCSA-N 0.000 claims abstract description 61
- 108010007859 Lisinopril Proteins 0.000 claims abstract description 52
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims abstract description 12
- 229930195725 Mannitol Natural products 0.000 claims abstract description 12
- 239000000594 mannitol Substances 0.000 claims abstract description 12
- 235000010355 mannitol Nutrition 0.000 claims abstract description 12
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims abstract description 9
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims abstract description 9
- 239000008108 microcrystalline cellulose Substances 0.000 claims abstract description 9
- 229940016286 microcrystalline cellulose Drugs 0.000 claims abstract description 9
- 238000012986 modification Methods 0.000 claims abstract description 8
- 230000004048 modification Effects 0.000 claims abstract description 8
- 229920002472 Starch Polymers 0.000 claims abstract description 4
- 239000008107 starch Substances 0.000 claims abstract description 4
- 235000019698 starch Nutrition 0.000 claims abstract description 4
- 239000000203 mixture Substances 0.000 claims description 31
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 18
- 239000002245 particle Substances 0.000 claims description 16
- 235000019359 magnesium stearate Nutrition 0.000 claims description 9
- 238000009826 distribution Methods 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 4
- 238000007907 direct compression Methods 0.000 claims description 3
- 238000004090 dissolution Methods 0.000 description 14
- 229920000881 Modified starch Polymers 0.000 description 8
- 239000013543 active substance Substances 0.000 description 8
- 229920002261 Corn starch Polymers 0.000 description 7
- 235000019759 Maize starch Nutrition 0.000 description 7
- 239000008363 phosphate buffer Substances 0.000 description 6
- 230000000052 comparative effect Effects 0.000 description 5
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 4
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 206010020772 Hypertension Diseases 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 235000019700 dicalcium phosphate Nutrition 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 229960003883 furosemide Drugs 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-UHFFFAOYSA-N 0.000 description 2
- 206010007559 Cardiac failure congestive Diseases 0.000 description 2
- 206010019280 Heart failures Diseases 0.000 description 2
- 102000004270 Peptidyl-Dipeptidase A Human genes 0.000 description 2
- 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 2
- 239000013066 combination product Substances 0.000 description 2
- 229940127555 combination product Drugs 0.000 description 2
- 238000007906 compression Methods 0.000 description 2
- 230000006835 compression Effects 0.000 description 2
- 230000001882 diuretic effect Effects 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- WSVLPVUVIUVCRA-KPKNDVKVSA-N Alpha-lactose monohydrate Chemical compound O.O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O WSVLPVUVIUVCRA-KPKNDVKVSA-N 0.000 description 1
- JZUFKLXOESDKRF-UHFFFAOYSA-N Chlorothiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O JZUFKLXOESDKRF-UHFFFAOYSA-N 0.000 description 1
- 108010061435 Enalapril Proteins 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 206010033109 Ototoxicity Diseases 0.000 description 1
- 208000004880 Polyuria Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000008351 acetate buffer Substances 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 231100001124 band 1 compound Toxicity 0.000 description 1
- 231100001126 band 3 compound Toxicity 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 238000007922 dissolution test Methods 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 229940088679 drug related substance Drugs 0.000 description 1
- 229960000873 enalapril Drugs 0.000 description 1
- GBXSMTUPTTWBMN-XIRDDKMYSA-N enalapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(O)=O)CC1=CC=CC=C1 GBXSMTUPTTWBMN-XIRDDKMYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229960002003 hydrochlorothiazide Drugs 0.000 description 1
- 230000001077 hypotensive effect Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229960001375 lactose Drugs 0.000 description 1
- 229960001021 lactose monohydrate Drugs 0.000 description 1
- 238000007561 laser diffraction method Methods 0.000 description 1
- 229960001855 mannitol Drugs 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 231100000262 ototoxicity Toxicity 0.000 description 1
- 238000003921 particle size analysis Methods 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 238000000634 powder X-ray diffraction Methods 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- FMLHTZVGNSACKP-UHFFFAOYSA-N pyridin-2-ylsulfonylurea Chemical compound NC(=O)NS(=O)(=O)C1=CC=CC=N1 FMLHTZVGNSACKP-UHFFFAOYSA-N 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 230000002207 retinal effect Effects 0.000 description 1
- 238000001507 sample dispersion Methods 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/401—Proline; Derivatives thereof, e.g. captopril
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/64—Sulfonylureas, e.g. glibenclamide, tolbutamide, chlorpropamide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
Definitions
- the present invention relates to combination preparation of ACE inhibitor lisinopril and loop diuretic torasemide and pharmaceutical use therof.
- Lisinopril one of ACE inhibitors, is primarily used in treatment of hypertension, congestive heart failure, heart attacks and in preventing renal and retinal complications of diabetes.
- Lisinopril is the lysine-analog of enalapril.
- lisinopril is not a prodrug and is excreted unchanged in the urine. In cases of overdosage, it can be removed from circulation by dialysis.
- Lisinopril belongs to BCS class III, which means that the drug substance has high solubility, but absorption is limited by the permeation rate.
- ACE inhibitors have a hypotensive effect in combination with loop diuretics, such as furosemide and piretanid, in low dosage.
- Lisinopril can be used in conjunction with the diuretic hydrochlorothiazide and drugs that combine these two medications are commercially available.
- Torasemide is a pyridine-sulfonyl urea type loop diuretic mainly used in the management of edema associated with congestive heart failure. It is also used at low doses for the management of hypertension. Compared with other loop diuretics, torasemide has a more prolonged diuretic effect than equipotent doses of furosemide and relatively decreased potassium loss.
- Torasemide has been classified as BCS class I drug (high solubility and high permeability) up to a maximum dose of 40 mg. Solubility of torasemide is pH dependent and the lowest solubility is observed between pH 4 and pH 6.
- solubility of torasemide depends on the manufacturing parameters, polymorphic form, particle size and shape. Therefore not all forms of torasemide are appropriate for the preparation of rapidly dissolving formulation.
- Lisinopril as an active substance and while is present in a commercial lisinopril preparation dissolves well. However, if lisinopril and torasemide were combined together in one preparation and the same excipients as for the known preparations of torasemide and lisinopril were used, much lower dissolution profile was observed.
- Dissolution profiles for the tablets prepared in comparative example 1 were significantly lower in comparison with each commercial tablet preparation containing single active substances, torasemide or lisinopril respectively. Changing of the proportion between calcium hydrogen phosphate and mannitol caused sticking of the tablet mass to punches and compression of the tablets was not possible.
- the object of the present invention is to provide rapidly dissolving preparation of torasemide and lisinopril combination product. More specifically, the invention relates to the composition comprising torasemide modification I, lisinopril dihydrate, microcrystalline cellulose, starch, mannitol and glidant, e.g. magnesium stearate.
- composition may contain other active ingredients and excipients.
- the composition according to the present invention has a form of tablet, manufactured by direct compression.
- a form of tablet manufactured by direct compression.
- at least 85% of torasemide and at least 85% of lisinopril is dissolved in 15 minutes in phosphate buffer of pH 4.5 using paddle apparatus at 75 rpm at 37.0 ⁇ 0.5°C.
- Dissolution studies presented in the present invention were performed using buffer solutions described in European Pharmacopoeia 8.0, i.e. acetate buffer pH 4.5 and phosphate buffer pH 6.8 using methodology described in European Pharmacopoeia 8.0 chapter 2.9.3 "Dissolution test for solid dosage forms" in apparatus 2 (paddle apparatus). 500 ml of the medium in each testing vessel was used. Content of the active substances torasemide and lisinopril was evaluated using validated HPLC method using UV/VIS detector. Percent dissolution was calculated as an average value from 6 replicate dissolution experiments.
- the composition according to the present invention has a form of tablet, manufactured by direct compression and more than 85% of the lisinopril and more than 85% of torasemide is dissolved in 15 minutes in phosphate buffer of pH 6.8 using paddle apparatus at 75 rpm at 37.0 ⁇ 0.5°C.
- particle size distribution of torasemide is represented by d(0.5) from 20 ⁇ m to 80 ⁇ m and d(0.9) below 100 ⁇ m, which means that 50% of torasemide particles by volume have diameter from 20 ⁇ m to 80 ⁇ m and 90% of torasemide particles have diameter below 100 ⁇ m.
- Particle size distribution data are usually reported as cumulative undersize distribution.
- the symbol d is used to denote the particle size, which in turn is defined as the diameter of a volume-equivalent sphere.
- d(0.5) denotes the volume fraction undersize at the particle size d.
- the particle sizes at the undersize values of 10%, 50% and 90% are frequently used.
- Particle size value d(0.5) is also known as the median particle size.
- Particle size of torasemide was measured using laser diffraction method described in European Pharmacopoeia 8.0 chapter 2.9.31 "Particle size analysis by laser light diffraction” using Mastersizer 2000 apparatus with Hydro 2000 S sample dispersion unit .
- particle size distribution of torasemide is represented by d(0.5) from 50 ⁇ m to 80 ⁇ m and d(0.9) below 100 ⁇ m.
- Torasemide shows polymorphism and several crystal modifications of torasemide are known ( Acta Cryst., 1978, pp. 2659-2662 and Acta Cryst., 1978, pp. 1304-1310 ).
- torasemide refers to torasemide modification I, which x-ray powder diffraction pattern corresponds to the pattern of modification I, as depicted in WO 2004/089904 A2 .
- Torasemide crystal modification I is stable and does not convert to other crystals forms.
- the tablet according to the present invention comprises lisinopril and torasemide in pharmaceutically effective amounts.
- Content of each active substance refers to anhydrous substance, unless otherwise specified.
- one tablet contains 10 mg of lisinopril and 10 mg of torasemide as the active substances.
- one tablet contains 20 mg of lisinopril and 10 mg of torasemide as the active substances.
- one tablet contains 10 mg of lisinopril and 5 mg of torasemide as the active substances.
- one tablet contains 20 mg of lisinopril and 5 mg of torasemide as the active substances.
- One tablet contained 20 mg of lisinopril and 10 mg of torasemide and had a total weight of 450 mg.
- Tablet weight was 210 mg and content of lisinopril and torasemide in one tablet was 10 mg and 5 mg respectively Dissolution profile of the obtained tablets were tested using paddle apparatus and phosphate buffer of pH 6.8 at 75 rpm and 37.0 ⁇ 0.5°C. Only 69% of torasemide and 77% of lisinopril were dissolved in 15 minutes.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Preparation (AREA)
Priority Applications (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| LTEP15003387.6T LT3173075T (lt) | 2015-11-27 | 2015-11-27 | Ace inhibitoriaus ir kilpinio diuretiko farmacinė kompozicija |
| ES15003387T ES2703376T3 (es) | 2015-11-27 | 2015-11-27 | Preparación de combinación farmacéutica de inhibidor de ACE y diurético de bucle |
| EP15003387.6A EP3173075B1 (fr) | 2015-11-27 | 2015-11-27 | Préparation pharmaceutique combinée constituée d'un inhibiteur ace et diurétique de l'anse |
| SI201530541T SI3173075T1 (sl) | 2015-11-27 | 2015-11-27 | Farmacevtski kombinacijski pripravek inhibitorja ACE in diuretika zanke |
| DK15003387.6T DK3173075T3 (en) | 2015-11-27 | 2015-11-27 | PHARMACEUTICAL COMBINATION PREPARATION OF ACE INHIBITOR AND LOOPDIURETIC |
| PL15003387T PL3173075T3 (pl) | 2015-11-27 | 2015-11-27 | Farmaceutyczny preparat złożony inhibitora ACE i diuretyku pętlowego |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP15003387.6A EP3173075B1 (fr) | 2015-11-27 | 2015-11-27 | Préparation pharmaceutique combinée constituée d'un inhibiteur ace et diurétique de l'anse |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EP3173075A1 true EP3173075A1 (fr) | 2017-05-31 |
| EP3173075B1 EP3173075B1 (fr) | 2018-09-26 |
Family
ID=54754405
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP15003387.6A Active EP3173075B1 (fr) | 2015-11-27 | 2015-11-27 | Préparation pharmaceutique combinée constituée d'un inhibiteur ace et diurétique de l'anse |
Country Status (6)
| Country | Link |
|---|---|
| EP (1) | EP3173075B1 (fr) |
| DK (1) | DK3173075T3 (fr) |
| ES (1) | ES2703376T3 (fr) |
| LT (1) | LT3173075T (fr) |
| PL (1) | PL3173075T3 (fr) |
| SI (1) | SI3173075T1 (fr) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0215357A2 (fr) | 1985-09-09 | 1987-03-25 | Hoechst Aktiengesellschaft | Préparation pharmaceutique pour le traitement de l'hypertension |
| US4822807A (en) * | 1985-08-17 | 1989-04-18 | Boehringer Mannheim Gmbh | Pharmaceutical composition containing a stable modification of torasemide |
| WO2004089904A2 (fr) | 2003-04-07 | 2004-10-21 | Torcan Chemical Ltd. | Preparation de torasemide |
-
2015
- 2015-11-27 PL PL15003387T patent/PL3173075T3/pl unknown
- 2015-11-27 SI SI201530541T patent/SI3173075T1/sl unknown
- 2015-11-27 EP EP15003387.6A patent/EP3173075B1/fr active Active
- 2015-11-27 LT LTEP15003387.6T patent/LT3173075T/lt unknown
- 2015-11-27 DK DK15003387.6T patent/DK3173075T3/en active
- 2015-11-27 ES ES15003387T patent/ES2703376T3/es active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4822807A (en) * | 1985-08-17 | 1989-04-18 | Boehringer Mannheim Gmbh | Pharmaceutical composition containing a stable modification of torasemide |
| EP0215357A2 (fr) | 1985-09-09 | 1987-03-25 | Hoechst Aktiengesellschaft | Préparation pharmaceutique pour le traitement de l'hypertension |
| WO2004089904A2 (fr) | 2003-04-07 | 2004-10-21 | Torcan Chemical Ltd. | Preparation de torasemide |
Non-Patent Citations (5)
| Title |
|---|
| ACTA CRYST., 1978, pages 1304 - 1310 |
| ACTA CRYST., 1978, pages 2659 - 2662 |
| ANOMYMOUS: "DEMADEX (torsemide) TABLETS", August 2012 (2012-08-01), internet, pages 1 - 13, XP055250151, Retrieved from the Internet <URL:http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/020136s014lbl.pdf> [retrieved on 20160215] * |
| ANONYMOUS: "LISINOPRIL-PS tablets 2.5 mg, 5 mg, 10 mg, 20 mg.", May 2012 (2012-05-01), internet, pages 1 - 4, XP055250126, Retrieved from the Internet <URL:https://www.betterhealth.vic.gov.au/~/media/bhc/files/medicine%20guides%20library/10/cmi10360.pdf> [retrieved on 20160215] * |
| ANONYMOUS: "Package Leaflet: Information for the User Lisinopril 2", September 2014 (2014-09-01), internet, pages 1 - 7, XP055250130, Retrieved from the Internet <URL:https://www.medicines.org.uk/emc/PIL.31134.latest.pdf> [retrieved on 20160215] * |
Also Published As
| Publication number | Publication date |
|---|---|
| SI3173075T1 (sl) | 2019-02-28 |
| DK3173075T3 (en) | 2019-01-21 |
| EP3173075B1 (fr) | 2018-09-26 |
| ES2703376T3 (es) | 2019-03-08 |
| PL3173075T3 (pl) | 2019-04-30 |
| LT3173075T (lt) | 2019-01-10 |
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